The present invention relates to a method for testing a container for tightness. Moreover, the invention relates to a corresponding computer program product.
The method of testing tightness with positive pressure or negative pressure (“vacuum”) is applied as a technical method within quality control of pharmaceutical containers in particular and closed containers in general. Particularly within the scope of primary packaging of medicaments, testing tightness by means of a vacuum is a fundamental nondestructive testing method because it is universally applicable.
To this end, a container (vial, ampoule, etc.) that was filled and sealed under atmospheric pressure (or a partial vacuum) is placed in a vacuum in a closed chamber during the testing process; i.e., the space around the container is evacuated and then locked by a valve. Subsequently, a potential pressure change within a certain test time is measured. If the pressure remains constant, this indicates the tightness of the chamber and the inserted container. If the pressure increases during the test time, this indicates a leaky container in the case of a tight test system. The gaseous content (usually air) flows out through leaks such as holes, tears, foreign bodies on the plug, etc., until the pressure between the interior of the container and the vacuum chamber has equalized. In the case of a liquid content, emerging liquid can likewise be detected as a pressure increase if the vacuum in the test chamber lies under the saturation vapor pressure (23 mbar for water at 20° C.) such that the liquid boils.
A similar functionality, which is virtually inverted to the vacuum testing, is the tightness test by means of positive pressure. The advantage herein lies in the greater applicable pressure range. However, a disadvantage consists of the potential risk of leaks (e.g. tears) being sealed by the positive pressure. Moreover, already damaged containers run the increased risk of bursting under the higher pressure difference. Moreover, the method is not suitable for identifying leaks due to liquid (test above saturation vapor pressure and pressure difference from outside to inside).
For this fundamental type of tightness test based on pressure changes, there are a number of patent applications, specialist publications and standards. The above-described procedure is prior art and disclosed.
Currently, the following evaluations are conventional in the case of tightness tests based on a vacuum or positive pressure. Thus, the integral pressure change Δp (in Pa) from start to end of the measurement phase with the time duration t, or the pressure increase over time Δp/Δt (in Pa/s), is evaluated in e.g. the ASTM F2338-09 standard and in the publication Wolf et al., Vacuum Decay Container/Closure Integrity Testing Technology. Part 1. ASTM F2338-09 Precision and Bias Studies. PDA J Pharm Sci Technol 2009, 63, 5, 472-488, and in the tightness testing appliance CETATEST515 by CETA Testsysteme GmbH.
The leakage rate Q derived from the pressure measurement is the p·V throughput per unit time of a specific fluid (in this case air) through a leak under certain conditions, usually at a pressure difference of 1013 mbar and a temperature of 20° C. (“helium standard conditions”):Q=Δ(p·V)/Δt (amount of gas per unit time [Q]=mbar·l/s)  (Formula 1)
In the tightness test, the essential volume is the residual volume VR, which corresponds to the chamber volume (including possible channels up to the pressure sensor) minus the volume of the test object.
If the leakage rate is expressed as a volumetric flow rate in standard ml/min, the unit is related to normal conditions (DIN 1343: 0° C., 1013 mbar). The reference to a standard reference atmosphere (DIN 1945-1: 20° C., 1 bar, dry air) is also conventional.
A stable measurement state is rendered more difficult by outgassing or temperature effects during the evacuation and by subsequently flowing air from capillaries such as e.g. threads. Such effects are reduced by a stabilization phase between the evacuation of the chamber and the measurement phase.
On account of environmental factors such as humidity, temperature and atmospheric pressure, even the pressure profile of a tight container may vary between a plurality of measurements. Connected therewith are variations of a tightness reference value determined therefrom and of an acceptance criterion (good/bad criterion), which lies at a certain distance above the tightness reference value. For the purposes of compensating such drifts, U.S. Pat. No. 6,202,477 relating to an automated vacuum tightness test has disclosed the method of a “dynamic reference signal”. Here, the tightness reference value is formed continuously by averaging the pressure changes of the last n test objects evaluated to be good and the acceptance criterion (“reference signal”) is updated. An additional, fixed upper limit prevents variations of the reference signal that are too great.
In addition to the evaluation of the pressure increase (“fine leak test”), the tightness test process usually contains an additional “coarse leak test”, carried out beforehand and/or afterward, as disclosed in e.g. U.S. Pat. No. 8,544,315B2. In so doing, the measurement chamber is unified with a second volume (e.g. the rear space of a valve), in which a deviating known pressure level is set. From knowledge of the initial pressures and the equalization pressure after the volume unification, an evaluation is carried out as to whether the container has such a large leak that the interior of the container was already completely evacuated during the evacuation phase and it was no longer possible to identify a fine leak due to lack of pressure difference in relation to the measurement chamber.
The possibility of detecting liquid leaks by means of a pressure increase test is disclosed in U.S. Pat. No. 8,554,315B2 and further patent documents listed therein.